Julinda Mehilli, Julius Steffen, Tanja Rudolph, Magda Haum, Christina Giannini, Konstantin Stark, Hüseyin Ince, Lenard Conradi, Michael Joner, Andreas Schäfer, Ann-Katrin Karcher, Martin Landt, Matti Adam, Holger Thiele, Tobias Geisler, David Jochheim, Christian Hagl, Uwe Zeymer, Stephan Windecker, Steffen Massberg, REBOOT-PARADOX-Trial Investigators
Although the effect of TAVR on mortality remains unresolved, these findings support an individualized strategy with close surveillance and timely TAVR upon clinical deterioration in selected patients with pLFLG AS. Adequately powered randomized trials are needed to define the effect of early TAVR on prognosis. (accuRate Evaluation of Benefit with Optimal medical treatment with or withOut Transcatheter valve repair of PARADOXical low flow low gradient aortic stenosis [REBOOT-PARADOX Trial]; NCT03863132).
BACKGROUND: Paradoxical low-flow, low-gradient (pLFLG) aortic stenosis (AS) has an adverse prognosis in comparison to other AS subtypes. Transcatheter aortic valve replacement (TAVR) has never been compared with optimal medical therapy (OMT) alone in a dedicated randomized trial in this population.
OBJECTIVES: The trial sought to determine whether TAVR added to OMT reduces all-cause mortality in symptomatic patients with pLFLG AS.
METHODS: In this multicenter, open-label trial, patients with symptomatic pLFLG AS (aortic valve area ≤1.0 cm2, mean gradient <40 mm Hg, stroke volume index <35 mL/m2, ejection fraction ≥50%) were randomly assigned 2:1 to TAVR plus OMT or OMT alone. The primary endpoint was all-cause death, assessed 2 years after enrollment of the last patient. Enrollment was stopped prematurely for slow recruitment.
RESULTS: Of 783 planned patients, 120 (median age 82 years; 53.3% women) were randomized (80 TAVR, 40 OMT). A total of 19 OMT patients eventually crossed over to TAVR, most for symptom progression. The primary endpoint occurred in 29.0% vs 37.1% (HR: 0.83; 95% CI: 0.41-1.66; P = 0.60), and 5-year mortality was 44.9% vs 56.6% (HR: 0.76; 95% CI: 0.43-1.35; P = 0.35). TAVR was associated with improved symptoms (NYHA functional class I/II at 1 year, 83.0% vs 59.0%) and lower cumulative incidence of first endpoint-related rehospitalizations, and there were no differences in functional capacity or quality of life.
CONCLUSIONS: Although the effect of TAVR on mortality remains unresolved, these findings support an individualized strategy with close surveillance and timely TAVR upon clinical deterioration in selected patients with pLFLG AS. Adequately powered randomized trials are needed to define the effect of early TAVR on prognosis. (accuRate Evaluation of Benefit with Optimal medical treatment with or withOut Transcatheter valve repair of PARADOXical low flow low gradient aortic stenosis [REBOOT-PARADOX Trial]; NCT03863132).